Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

The performance of interferon gamma release assays in patients with nontuberculous mycobacterial infection: a systematic review and meta-analysis.

BACKGROUND: The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). METHODS: Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. RESULTS: A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. CONCLUSIONS: The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies.

Interferon-γ release assay and mantoux response in infants with tuberculous meningitis in low and intermediate burden countries.

AIM: Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA. METHODS: Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study. RESULTS: A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results. CONCLUSIONS: In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM.

Risk factors for death in tuberculosis patients requiring ICU care.

The prognostic factor for in-hospital mortality in tuberculosis (TB) patients requiring intensive care unit (ICU) care remains unclear. Therefore, a retrospective study was conducted aiming to estimate the in-hospital mortality rate and the risk factors for mortality in a high-burden setting. All patients with culture-confirmed TB that were admitted to the ICU of the hospital between March 2012 and April 2019 were identified retrospectively. Data, such as demographic characteristics, comorbidities, laboratory measures and mortality, were obtained from medical records. The Cox proportional hazards regression model was used to identify prognostic factors that influence in-hospital mortality. A total of 82 ICU patients with confirmed TB were included in the analysis, and 22 deaths were observed during the hospital stay, 21 patients died in the ICU. In the multivariable model adjusted for sex and age, the levels of serum albumin and white blood cell (WBC) count were significantly associated with mortality in TB patients requiring ICU care (all P < 0.01), the hazard ratios were 0.8 (95% confidence interval (CI): 0.7-0.9) per 1 g/l and 1.1 (95% CI: 1.0-1.2) per 1 × 109/l, respectively. In conclusion, in-hospital mortality remains high in TB patients requiring ICU care. Low serum albumin level and high WBC count significantly impact the risk of mortality in these TB patients in China.

Factors associated with negative pleural adenosine deaminase results in the diagnosis of childhood pleural tuberculosis.

BACKGROUND: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB). METHODS: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results. RESULTS: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ2 = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB. CONCLUSION: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.

The prevalence, diagnosis and surgical risk factors of spinal tuberculosis in children.

OBJECTIVE: To date, the burden of childhood spinal TB in China has not been estimated, and current treatment is hindered by a lack of evidence. This study aimed to review our experience of childhood spinal TB. METHODS: We reviewed the medical records of paediatric patients (≤15 years) admitted for spinal TB (confirmed or possible) at Shandong Provincial Chest Hospital from January 2006 to December 2019. Demographic, clinical, laboratory and radiological data were collected from medical records and analysed retrospectively. RESULTS: Seventy-two patients were diagnosed with spinal TB. 45 were male (62.5%), and 27 female (37.5%), with a mean age of 8.42 ± 4.47 (SD) years. During this 14-year period, the overall prevalence of spinal TB among childhood TB was 4.5%. T-SPOT.TB, AFB smear, mycobacterial culture, TB RT-PCR and biopsies were positive in 29.6%, 14.3%, 23.3%, 43.8% and 88.5% of assayed patients, respectively. The overall surgical rate of the studied patients was 40.3%. The requirement of surgery in childhood spinal TB was associated with pulmonary TB (OR = 4.000, 95% CI: 1.197, 13.367). CONCLUSION: Spinal TB in children cannot be neglected. It remains a severe problem to public health, and more attention should be paid to initiating treatment early.

OBJECTIF: A ce jour, la charge de la tuberculose (TB) vertébrale infantile en Chine n'a pas été estimée et le traitement actuel est entravé par un manque de données. Cette étude visait à passer en revue notre expérience de la TB vertébrale infantile. MÉTHODES: Nous avons examiné les dossiers médicaux des patients pédiatriques (≤15 ans) admis pour une TB vertébrale (confirmés ou possibles) au Shandong Provincial Chest Hospital de janvier 2006 à décembre 2019. Les données démographiques, cliniques, de laboratoire et radiologiques ont été recueillies à partir des dossiers médicaux et analysées rétrospectivement. RÉSULTATS: Soixante-douze patients ont reçu un diagnostic de TB vertébrale. 45 étaient de sexe masculin (62,5%) et 27 de sexe féminin (37,5%), avec un âge moyen de 8,42 ± 4,47 (DS) ans. Au cours de cette période de 14 ans, la prévalence globale de la TB vertébrale dans la TB infantile était de 4,5%. T-SPOT.TB, frottis de BAR, culture mycobactérienne, RT-PCR, TB et biopsies étaient positifs chez 29,6%, 14,3%, 23,3%, 43,8% et 88,5% des patients testés, respectivement. Le taux chirurgical global chez les patients étudiés était de 40,3%. La nécessité d'une intervention chirurgicale dans la TB vertébrale infantile était associée à la TB pulmonaire (OR: 4,000, IC95%: 1,197 - 13,367). CONCLUSION: La TB vertébrale chez l'enfant ne peut pas être négligée. Elle demeure un grave problème de santé publique et il faudrait accorder plus d'attention à l'initiation précoce du traitement.

Treatment delay in childhood pleural tuberculosis and associated factors.

BACKGROUND: Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances the transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among childhood pleural TB patients in China. METHODS: Between January 2006 and December 2019, consecutive patients aged ≤15 years with definite or possible pleural TB were included for analysis. Treatment delay duration was defined as the time interval from the onset of symptoms to treatment initiation and was stratified into two categories: < 30 days, ≥30 days (median delay day is 30 days). The electronic medical records of children were reviewed to obtain demographic characteristics, clinical characteristics, laboratory examinations, and radiographic findings. Univariate and multivariate logistic regressions were used to explore the factors associated with treatment delay in patients. RESULTS: A total of 154 children with pleural TB were included, with a mean age of 12.4 ± 3.3 years. The median treatment delay was 30 days (interquartile range, 10-60 days) and 51.3% (n = 79) of patients underwent a treatment delay. Multivariate analysis revealed that heart rate (≤92 beats/min, age-adjusted OR = 2.503, 95% CI: 1.215, 5.155) and coefficient of variation of red cell distribution width (RDW-CV, ≥12.9%, age-adjusted OR = 4.705, 95% CI: 2.048, 10.811) were significant risk factors for treatment delays in childhood pleural TB. CONCLUSION: Our findings suggested that a significant treatment delay occurs among children with pleural TB in China. Patients with a low heart rate or a high RDW-CV experienced delays in the initiation of anti-TB therapy. Therefore, well awareness of the associations between clinical characteristics and treatment delay may improve the management of children with pleural TB and enable us to develop preventive strategies to reduce the treatment delay.

Comparison of computed tomography-guided percutaneous needle biopsy and endobronchial biopsy in the diagnosis of multifocal pulmonary lesions.

BACKGROUND: The retrospective study aimed to compare computed tomography (CT)-guided percutaneous needle biopsy (PNB) and endobronchial biopsy (EB) in the diagnosis of multifocal pulmonary lesions with endobronchial involvement. METHODS: Between November 2014 and June 2017, consecutive patients who had underwent both CT-guided PNB and EB via bronchoscopy for diagnosis of pulmonary lesions were evaluated retrospectively. Tissue samples were submitted for pathological examination, acid-fast bacilli, TB RT-PCR, and mycobacterial culture. Sensitivities of the two methods alone or in combination were calculated and compared using Fisher's exact test. RESULTS: Sixty-seven patients (46 men and 21 women) were enrolled and could be diagnosed (32 malignant, 18 TB, and 17 benign). A final diagnosis of either malignant or TB diseases was made in 34 (68.0%) patients for CT-guided PNBs, 19 (38.0%) patients for EBs, and 42 (84.0%) patients for the combination of both methods. Further statistical analysis showed significant difference in sensitivity between CT-guided PNBs, or the combination of both methods, and EBs (all P < 0.05), and no difference between CT-guided PNBs and the combination (P > 0.05). However, the combination of both methods appears to have the highest sensitivity in the detection of malignancies or TB diseases. CONCLUSION: Compared with EB, CT-guided PNB has a high diagnostic yield for the detection of TB and malignancy in patients with multifocal pulmonary lesions with endobronchial involvement. When the two biopsies are combined, it appears to provide an incremental diagnostic value for the pulmonary lesions.

Comparison of enzyme-linked immunosorbent assay with indirect immunofluorescence assay for the diagnosis of Mycoplasma pneumoniae infection.

BACKGROUND: The study aimed to compare enzyme-linked immunosorbent assay (ELISA) with indirect immunofluorescence assay (IFA) in the diagnosis of Mycoplasma pneumoniae infection. METHODS: From March 2016 to May 2017, 180 patients suspected with M. pneumoniae infection were enrolled. The SeroMP kit using ELISA and PNEUMOSLIDE kit using IFA were performed in parallel to detect the IgM antibodies against M. pneumoniae. Cohen's kappa statistics were used to assess the agreement between the ELISA and IFA assays, multivariate logistic regression analysis was used to evaluate risk factors for the discordance between the ELISA and IFA assays. RESULTS: The mean age of the enrolled subjects was 46.6 ± 21.1 years. For detection of M. pneumoniae infection, the positivities of the ELISA and IFA assays were 15.6% (95% CI: 11.0%, 21.6%) and 10.0% (95% CI: 6.4%, 15.3%), respectively. The total positivity was 19.4% (95% CI: 14.3%, 25.8%). The agreement between the ELISA and IFA assays was low (κ = 0.117, P < 0.001). Variables associated with discordant results between ELISA and IFA assays in multivariate analysis were as follows: male (OR: 0.366; 95% CI: 0.149, 0.899; P < 0.05), age (>33 years old; OR: 0.313; 95% CI: 0.129, 0.758; P < 0.05). CONCLUSION: In detection of M. pneumoniae infection, low agreement was found in IgM assays between the ELISA and IFA methods, female and younger age were significant risk factors for the discordance. A combination of ELISA and IFA tests would be recommended, in order to detect more patients suspected of M. pneumoniae infection in clinical practice.

Total delay in treatment among tuberculous meningitis patients in China: a retrospective cohort study.

BACKGROUND: Currently, there is limited data on the risk factors associated with treatment delay in tuberculous meningitis (TBM). This study aimed to assess the duration of delay in the treatment TBM and to investigate its determinants. METHODS: During the period from September 2009 to February 2016, a retrospective cohort study of consecutive TBM patients admitted to our hospital was conducted to determine the risk factors associated with treatment delay in TBM. Treatment delay duration was defined as the time interval from onset of symptoms (by patient recall) to initiation of treatment and was stratified into two categories: ≤ 20 days, >20 days (median delay day is 20 days). Data collected included demography, comorbidity, cerebrospinal fluid (CSF) examinations and others. Univariable and multivariable logistic regression analysis was used to evaluate the determinants of treatment delay. RESULTS: A total of 161 TBM patients were included in our study, all were confirmed by CSF mycobacterial culture. The median treatment delay for all patients included in the study was 20 days [interquartile range, 14-60 days]. Multivariate analysis revealed that age (≤21 years old, OR = 0.202, 95% CI: 0.079, 0.521), fever (OR = 0.414, 95% CI: 0.180, 0.952), and headache (OR = 0.204, 95% CI: 0.095, 0.442) had significantly lower risk for treatment delay, while multiple healthcare contact (>3 times) (OR = 3.938, 95% CI: 1.326, 11.691) as well as CSF chloride (>111 mmol/L) (OR = 2.479, 95% CI: 1.143, 5.377) had significantly higher risk of the delay. CONCLUSIONS: Our findings indicate that multiple healthcare contact and high CSF chloride predict the risk of long delay, while young age, fever and headache are associated with short delay. Maintained focus on awareness of TBM in the population and in healthcare systems, and continuous implementation of diagnostic methods for TBM to detect the disease early, may reduce the mortality and morbidity.

The performance of interferon-gamma release assay in nontuberculous mycobacterial diseases: a retrospective study in China.

BACKGROUND: The interferon-gamma release assay (IGRA) is more specific than the tuberculin skin test to discriminate between tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases. Here we performed a retrospective study to evaluate the performance of the T-SPOT.TB in patients with NTM diseases. METHODS: Between March, 2013 and Nov, 2015, a total of 58 patients with NTM diseases had a T-SPOT.TB performed were enrolled, 30 patients had definite NTM diseases, 28 had probable diseases. Their clinicopathological characteristics were reviewed and analyzed. Cultures for mycobacteria were performed. The indirect proportion method with Löwenstein-Jensen (L-J) medium was used for first-line drug susceptibility test. T-SPOT.TB assay was performed according to the manufacturer's instructions. Data were expressed as mean ± standard deviation (continuous variables) and as numbers and percentages (categorical variables). The χ 2 test was used for comparisons between proportions. RESULTS: The average age was 51.8 ± 16.1 years (range 10 to 77 years), 58.6% (34/58) were male. 16.4% (9/55) were TB-PCR positive. 34 (58.6%) isolates were Mycobacterium intracellulare, ten (17.2%) were Mycobacterium chelonae and seven (12.1%) were Mycobacterium fortuitum. Fifty-two (89.7%) patients were NTM lung disease, five (8.6%) were pleural disease, and one (1.7%) lymphadenitis. The total positivity of T-SPOT.TB was 53.4% (31/58) among the whole group (probable and definite). For probable cases, the T-SPOT.TB assay was positive in 53.5% (15/28); for definite cases, 16 (53.3%) of 30 definite cases were positive. There was no statistical difference in the positivity rate between them (P < 0.01). CONCLUSIONS: In the study, we showed that a significant portion of NTM diseases were T-SPOT.TB positive in China. Although T-SPOT.TB is useful diagnostic method for differentiating TB from NTM diseases, in China, the IGRA assay show limited value in the discrimination. In addition, further research is needed to investigate the association between TB infection and treatment for NTM patients.

Evaluation of ALS assay of TB-SA for diagnosis of pulmonary tuberculosis.

The study evaluated tuberculosis specific antigen (TB-SA) antibody in lymphocyte supernatant (ALS) assay for diagnosis of pulmonary tuberculosis (PTB). The mean concentration of TB-SA ALS in PTB patients was significantly higher than that of two control groups (non-PTB patients and healthy subjects, P < 0.001). The area under the curve of the ALS assay were 0.960 (0.904-0.988, PTB vs healthy subjects), and were 0.822 (0.739-0.887, PTB vs Non-PTB patients), respectively. Our data indicated the ALS assay for TB-SA can be used as a screening test and is a useful adjunct to current tests for diagnosis of PTB.

Diagnostic Yield of Nucleic Acid Amplification Tests in Oral Samples for Pulmonary Tuberculosis: A Systematic Review and Meta-analysis.

The diagnostic accuracy of oral specimen nucleic acid amplification tests (NAATs) for pulmonary tuberculosis (PTB) remains controversial. We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including studies that reported the diagnostic yield of NAATs in oral samples for PTB diagnosis. The pooled estimates, including those of sensitivity and specificity, were calculated, and a meta-regression was performed to investigate heterogeneity, which was determined using χ2 and I² tests. A total of 23 articles were included, and the pooled sensitivity, specificity, and area under the curve of NAATs in oral samples for PTB diagnosis were 50% (95% CI, 37%-63%), 97% (95% CI, 93%-99%), and 0.89 (95% CI, 86%-92%; I 2 = 99%; chi-square, 169.61; P < .001), respectively. Our data demonstrated that NAATs using oral samples have a less satisfactory sensitivity and high specificity for PTB diagnosis. However, due to significant heterogeneity, such as heterogeneity in age, the results should be interpreted with caution.

Diagnostic value of the cerebrospinal fluid lipoarabinomannan assay for tuberculous meningitis: a systematic review and meta-analysis.

Objective: This systematic review aims to evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) lipoarabinomannan (LAM) assays in detecting tuberculous meningitis (TBM). Methods: A systematic review search was conducted in PubMed and five other databases up to April 2023. Studies that evaluated the diagnostic accuracy of CSF LAM assays were included with either definitive or composite reference standard used as the preferred reference standard. The quality of the included studies was assessed using the QUADAS-2 tool. We performed a bivariate random-effects meta-analysis and calculated the summary diagnostic statistics. Results: A total of six studies, including a sample size of 999, were included in the final analysis. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of CSF LAM for diagnosing TBM were determined to be 0.44 (95% CI: 0.31-0.58), 0.89 (95% CI: 0.81-0.93), and 0.76 (95% CI: 0.73-0.80), respectively. Significant heterogeneity was observed in both sensitivity (Q = 73.82, p < 0.01; I2 = 86.45, 95%CI: 79.64-93.27) and specificity (Q = 95.34, p < 0.01; I2 = 89.51, 95% CI: 84.61-94.42). Regression analysis indicated that the study design (retrospective vs. prospective) was associated with the heterogeneity of pooled sensitivity and specificity (all p < 0.05). Conclusion: Although more prospective studies are required to validate the role of the CSF LAM assay, current evidence supports that the performance of the CSF LAM assay is unsatisfactory for the TBM diagnosis. Additionally, the optimization of the CSF LAM assay (e.g., improvements in CSF collection and preparation methods) should be considered to improve its performance.

The role of Bacillus Calmette-Guérin administration on the risk of dementia in bladder cancer patients: a systematic review and meta-analysis.

Background: Previous cohort studies have found an association between Bacillus Calmette-Guérin (BCG) administration and incident dementia. In the systematic review and meta-analysis, we aimed to summarize the current evidence of the effect of BCG use on the risk of developing dementia. Methods: We searched six databases until 20 May 2023 for studies investigating the risk of dementia and BCG administration. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were conducted as well. Results: Of the 4,043 records initially evaluated, five articles were included for final analysis, with a total of 45,407 bladder cancer (BC) patients. All five studies were evaluated and rated as with high quality, and a low possibility of publication bias was indicated. A significant association between BCG and the incidence of dementia in BC patients was found in all five studies. Although a high heterogeneity (I2 = 84.5%, p < 0.001) was observed, the pooled HR was 0.55 (0.42-0.73), indicating that BCG exposure or treatment reduced the risk of incident dementia by 45%. Moreover, the sensitivity analysis showed good robustness of the overall effect with no serious publication bias. Conclusion: BCG administration is associated with a significantly lower risk of developing dementia. However, an epidemiological cohort is needed to establish a relationship between BCG use and incident dementia in the normal population. Once the relationship is confirmed, more people may benefit from the association. Systematic review registration: identifier: CRD42023428317.

The efficacy and safety of high-dose isoniazid-containing therapy for multidrug-resistant tuberculosis: a systematic review and meta-analysis.

Objectives: Accumulating evidence are available on the efficacy of high-dose isoniazid (INH) for multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to perform a systematic review and meta-analysis to compare clinical efficacy and safety outcomes of high-dose INH- containing therapy against other regimes. Methods: We searched the following databases PubMed, Embase, Scopus, Web of Science, CINAHL, the Cochrane Library, and ClinicalTrials.gov. We considered and included any studies comparing treatment success, treatment unsuccess, or adverse events in patients with MDR-TB treated with high-dose INH (>300 mg/day or >5 mg/kg/day). Results: Of a total of 3,749 citations screened, 19 studies were included, accounting for 5,103 subjects, the risk of bias was low in all studies. The pooled treatment success, death, and adverse events of high-dose INH-containing therapy was 76.5% (95% CI: 70.9%-81.8%; I2: 92.03%), 7.1% (95% CI: 5.3%-9.1%; I2: 73.75%), and 61.1% (95% CI: 43.0%-77.8%; I2: 98.23%), respectively. The high-dose INH administration is associated with significantly higher treatment success (RR: 1.13, 95% CI: 1.04-1.22; p < 0.01) and a lower risk of death (RR: 0.45, 95% CI: 0.32-0.63; p < 0.01). However, in terms of other outcomes (such as adverse events, and culture conversion rate), no difference was observed between high-dose INH and other treatment options (all p > 0.05). In addition, no publication bias was observed. Conclusion: In MDR-TB patients, high-dose INH administration is associated with a favorable outcome and acceptable adverse-event profile. Systematic review registration: identifier CRD42023438080.

Performance of Interferon-γ Release Assays in Patients with Mycobacterium kansasii Infection.

Objective: To evaluate the performance of interferon-γ release assays (IGRAs) in patients with Mycobacterium kansasii infection. Methods: Consecutive patients between May 2012 and June 2021 who had positive for mycobacterial cultures and who underwent IGRAs (T-SPOT.TB or QuantiFERON-TB Gold [QFT-G]) were included in the analysis. The IGRA positivity rates among patients with M. kansasii isolates were then calculated. If M. kansasii was identified in at least two sputum samples or in sterile samples, M. kansasii disease was then diagnosed. Otherwise, colonisation was considered. Results: During the study period, 54 patients with M. kansasii infection underwent T-SPOT.TB (n=48) or QFT-G (n=6) assays. The mean age was 44.1±13.4 years, 85.2% (46/54) were male. Eight patients were diagnosed with M. kansasii disease and another 46 patients were considered to have colonisation. Twenty-four patients (T-SPOT.TB, n=23; QFT-G, n=1) were positive for IGRAs, for an overall rate of 44.4% (24/54; T-SPOT.TB, 47.9% [23/48]; QFT-G, 16.7% [1/6]) for IGRAs, 25.0% (2/8) for M. kansasii disease, and 47.8% (22/46) for colonisation. Conclusion: Positive IGRA rates were relatively low in patients with M. kansasii infection. More efforts are required to improve the performance of IGRAs in diagnosing M. kansasii infection.

Prevalence of Culture-Confirmed Tuberculosis Among Patients with Nontuberculous Mycobacterial Disease.

Background: Currently, the prevalence of nontuberculous mycobacteria (NTM) strains isolated from mycobacterial cultures has been well characterized. However, the data on the prevalence of tuberculosis (TB) in patients with NTM disease remain unclear. Methods: Between January 2012 and August 2020, consecutive patients with positive mycobacterial cultures were included for analysis. The identification of Mycobacteria spp. was performed using the DNA array method or sequencing of 16S rDNA. NTM disease is diagnosed when the same infectious agent is identified in at least two sputum or is identified in sterile samples. Results: A total of 997 strains were isolated from 828 inpatients. Of them, 261 inpatients (31.5%) were diagnosed as NTM disease. The mean age of the 261 patients was 55.7 ±15.5 years old and 64.0% (n = 167) of them were male. The prevalence of culture-confirmed TB patients among patients with NTM disease was estimated as 8.0% (21/261). Conclusion: TB is common in NTM disease and caution should be taken when initiating the treatment of NTM disease.

The Sensitivity of Diagnostic Criteria of Marais S, et al. in Confirmed Childhood Tuberculous Meningitis.

BACKGROUND: To establish the sensitivity of the diagnostic criteria published by Marais and co-workers in 2010 for childhood tuberculous meningitis (TBM), a retrospective study on children with confirmed TBM was conducted. METHODS: Between January 2006 and December 2019, children consecutively diagnosed with TBM were recruited retrospectively at our center. TBM was defined in cases where any of the following criteria were met: the presence of acid-fast bacilli (AFB) in cerebrospinal fluid (CSF) microscopy, CSF nucleic acid amplification test (NAAT, +), or M.tuberculosis cultured from CSF. The demographic and clinical features of all enrolled patients were recorded including clinical characteristics, CSF findings, cerebral imaging features, and other evidence of TB. RESULTS: A total of 30 children with confirmed diagnosis of TBM over an 14-year period were recruited. The mean age of patients was 7.2 ± 5.1 years and 16 (53.3%) were male. The estimated mean diagnostic score was 12.7 ± 2.4. Twenty-three (76.7%; 95% CI: 59.1-88.2%) patients were classified as "probable TBM" according to the Marais criteria and 7 (23.3%; 95% CI: 11.8-40.9%) as "possible TBM." Further statistical analysis revealed significant differences in CSF scores between probable and possible TBM groups. Other variables reported at a relatively low frequency, such as symptoms and imaging features, made little contribution to TBM diagnosis according to the Marais criteria. CONCLUSION: Childhood TBM could be effectively identified by the criteria defined by Marais et al. However, further revision is required to ensure that the system is more sensitive and easier to perform in practice.